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HIV Rebound Is Predominantly Fueled by Genetically Identical Viral Expansions from Diverse Reservoirs

  1. Author:
    De Scheerder, Marie-Angélique
    Vrancken, Bram
    Dellicour, Simon
    Schlub, Timothy
    Lee, Eunok
    Shao,Wei
    Rutsaert, Sofie
    Verhofstede, Chris
    Kerre, Tessa
    Malfait, Thomas
    Hemelsoet, Dimitri
    Coppens, Marc
    Dhondt, Annemieke
    De Looze, Danny
    Vermassen, Frank
    Lemey, Philippe
    Palmer, Sarah
    Vandekerckhove, Linos

  2. Author Address

    HIV Cure Research Center, Department of General Internal Medicine, Ghent University Hospital, Ghent University, Ghent 9000, Belgium. Electronic address: marieangelique.descheerder@ugent.be., KU Leuven, Department of Microbiology and Immunology, Rega Institute, Laboratory of Evolutionary and Computational Virology, Herestraat 49, Leuven 3000 Belgium., KU Leuven, Department of Microbiology and Immunology, Rega Institute, Laboratory of Evolutionary and Computational Virology, Herestraat 49, Leuven 3000 Belgium; Spatial Epidemiology Laboratory (SpELL), Universit 233; Libre de Bruxelles, CP160/12 50, av. FD Roosevelt, 1050 Bruxelles, Belgium., University of Sydney, Faculty of Medicine and Health, Sydney School of Public Health, Sydney 2000, NSW, Australia., Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney 2145, NSW, Australia., Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD, USA., Aids Reference Laboratory, Ghent University Hospital, Ghent 9000, Belgium., Department of Hematology, Ghent University Hospital, Ghent 9000, Belgium., Department of Pulmonology, Ghent University Hospital, Ghent 9000, Belgium., Department of Neurology, Ghent University Hospital, Ghent 9000, Belgium., Department of Anesthesiology, Ghent University Hospital, Ghent 9000, Belgium., Department of Nephrology, Ghent University Hospital, Ghent 9000, Belgium., Department of Gastro-Enterology, Ghent University Hospital, Ghent 9000, Belgium., Department of Vascular Surgery, Ghent University Hospital, Ghent 9000, Belgium., HIV Cure Research Center, Department of General Internal Medicine, Ghent University Hospital, Ghent University, Ghent 9000, Belgium. Electronic address: linos.vandekerckhove@ugent.be.,
    1. Year: 2019
    2. Date: SEP 11
    3. Epub Date: 2019 08 27
  2. Journal: Cell host & microbe
    1. 26
    2. 3
    3. Pages: 347-+
  4. Type of Article: Article
  5. ISSN: 1931-3128
  1. Abstract:

    Viral rebound upon stopping combined antiretroviral therapy poses a major barrier toward an HIV cure. Cellular and anatomical sources responsible for reinitiating viral replication remain a subject of ardent debate, despite extensive research efforts. To unravel the source of rebounding viruses, we conducted a large-scale HIV-STAR (HIV-1 sequencing before analytical treatment interruption to identify the anatomically relevant HIV reservoir) clinical trial. We collected samples from 11 participants and compared the genetic composition of (pro)viruses collected under treatment from different cellular and anatomical compartments with that of plasma viruses sampled during analytical treatment interruption. We found a remarkably heterogeneous source of viral rebound. In addition, irrespective of the compartment or cell subset, genetically identical viral expansions played a significant role in viral rebound. Our study suggests that although there does not seem to be a primary source for rebound HIV, cellular proliferation is an important driver of HIV persistence and should therefore be considered in future curative strategies. Copyright © 2019 Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.chom.2019.08.003
  3. PMID: 31471273
  4. View record in Web of Science®
  5. WOS: 000485643600009
  6. PII : S1931-3128(19)30368-3

Library Notes

  1. Fiscal Year: FY2018-2019
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